Cu-Labeled Oxo-DO3A-conjugated trastuzumab and PCTA-conjugated trastuzumab

A bifunctional chelating agent (BFC) such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is often used to link a radionuclide with a monoclonal antibody (mAb) for the targeted imaging or radioimmunotherapy of cancers (1). However, a major limitation of using BFCs is that harsh reaction conditions such as high temperatures are required to facilitate the formation of the radionuclide-BFC complex (2). In addition, these complexes are not very stable . Ferreira et al. developed two BFCs, 1-oxa-4,7,10-triazacyclododecane--5-(4-nitrobenzyl)-4,7,10-triacetic acid (-NO(2)-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene--4-(4-nitrobenzyl)-3,6,9-triacetic acid (-NO(2)-Bn-PCTA), and showed that these chelators produced stable radiolabeled complexes with Cu under mild conditions ([Cu]-Oxo-DO3A and [Cu]-PCTA) (3). A preliminary biodistribution study in mice showed that, compared with [Cu]-DOTA, there was a lower accumulation of radioactivity in the liver with [Cu]-Oxo-DO3A and [Cu]-PCTA. It was also observed that clearance of the label from the kidneys of the animals was faster with [Cu]-PCTA than with either [Cu]-Oxo-DO3A or [Cu]-DOTA (3). Trastuzumab is a monoclonal antibody (mAb) that targets the HER2/ receptor, which is overexpressed in several types of cancer and is indicative of a poor prognosis for the patient (4). This mAb was approved by the United States Food and Drug Administration for the treatment of various cancers, and its radiolabeled form has been evaluated for the detection and radioimmunotherapy of the disease (5). Because the characteristics and applications of trastuzumab are well understood, Ferreira et al. investigated and compared the and properties of the Cu-labeled PCTA, Oxo-DO3A, and DOTA conjugates of this mAb (2).